Dexmedetomidine Attenuates Glutamate-Induced Cytotoxicity by Inhibiting the Mitochondrial-Mediated Apoptotic Pathway

Abstract

BackgroundGlutamate (GLU) is the most excitatory amino acid in the central nervous system and plays an important role in maintaining the normal function of the nervous system. During cerebral ischemia, massive release of GLU leads to neuronal necrosis and apoptosis. It has been reported that dexmedetomidine (DEX) possesses anti-oxidant and anti-apoptotic properties. The objective of this study was to investigate the effects of DEX on GLU-induced neurotoxicity in PC12 cells.Material/MethodsPC12 cells were treated with 20 mM GLU to establish an ischemia-induced injury model. Cell viability was accessed by MTT assay. MDA content and SOD activity were analyzed by assay kits. Apoptosis rate, ROS production, intracellular Ca2+ concentration, and MMP were evaluated by flow cytometry. Western blot analysis was performed to analyze expressions of caspase-3, caspase-9, cyt-c, bax, and bcl-2.ResultsPC12 cells treated with GLU exhibited reduced cell viability and increased apoptosis rates, which were ameliorated by pretreatment with DEX. DEX significantly increased SOD activity, reduced content of MDA, and decreased production of ROS in PC12 cells. In addition, DEX clearly reduced the level of intracellular Ca2+ and attenuated the decline of MMP. Moreover, DEX notably reduced expressions of caspase-3, caspase-9, cyt-c, and bax and increased expression of bcl-2.ConclusionsOur findings suggest that DEX can protect PC12 cells against GLU-induced cytotoxicity, which may be attributed to its anti-oxidative property and reduction of intracellular calcium overload, as well as its ability to inhibit the mitochondria-mediated apoptotic pathway.